The goals of this program continue to be the development of new synthetic methods for regiospecific preparation of naturally occurring polycyclic aromatic systems, especially those with anticancer activity. The proposed program will address a number of challenging problems in the area of polycyclic aromatic synthesis. Specifically, they will develop a route to an optically active 1(4H)- naphthalenone which can be used as an AB- synthon to 10-carbomethoxy anthracyclinones and use this material to synthesize aklavinone, the aglycone of the anticancer antibiotic aclacinomycin; develop a newly discovered oxygenation reaction, which accomplishes direct synthesis of 11-oxygenated anthracyclinones from hydronaphthacenones, and use the methodology to synthesize 11- hydroxylated anthracyclinones; develop methodology for construction of the cis-dihydroxy diketone fragment in tetracenomycin D and perform its total synthesis concurrent with syntheses of other tetracenomycins; develop a route for optically active total synthesis of angucycline antibiotics; develop new routes to 1(4H)-naphthalenones with substitution patterns that are appropriate for preparation of the benzo(a)naphthacenes G-2N and G-2A; employ a merged phthalide sulfone/polyketide strategy for optically active total synthesis of pradimicin C; develop methodology for optically active total synthesis of biaryl systems with substitution patterns found in naturally occurring polycyclic aromatic systems and utilize this procedure to accomplish an optically active total synthesis of calphostin D; develop methodology for synthesis of binaphthoquinones and bianthraquinones and use this to prepare representative examples such as skyrin, biphyscion and hypercin; develop new regiospecific annelation methodology for synthesis of uncommon phenolic substitution patterns as well asunoxygenated aromatic rings and use these procedures to accomplish optically active total syntheses of halen aquinones and rishirilides.